The present invention relates to an optical measuring instrument and especially to the optical measuring instrument suited for optical measurement of in vivo information.
The field of clinical medicine and brain science are eagerly expecting to have a measuring instrument which allows easy measurement of in-vivo blood circulation, hemodynamics and oxygen metabolism without giving much restriction to an examinee as a test object or being hazardous to a living body. In the case of cerebral measurement, for example, specific needs for such an instrument are found in the measurement and diagnosis of cerebral diseases such as brain infarction, intracerebral bleeding and dementia as well as high order cerebral functions such as thinking, language and bodily movement. Further, such objects for measurement are not restricted to the brain alone. Such a measuring instrument is needed for preventive diagnosis of such heart diseases as heart infarction on the pectoral region and viscera diseases related to kidney and liver on the abdominal region, as well as for the measurement of oxygen metabolism in limb muscles.
For simplicity, let us restrict the object to the cerebral region alone. In the measurement and diagnosis of intracerebral diseases or high order cerebral functions, it is necessary to specify the affected site or functional region clearly. This leads of the importance of cerebral image measurement. It goes without saying that the importance of image measurement is not restricted to the cerebral region. It also applies to the pectoral and abdominal region. Examples of showing its importance can be found in the positron emission tomographic equipment (PET), functional nuclear magnetic resonance tomographic equipment (fMRI) and magnetoencephalopgraphic equipment (MEG) which are placed in extensive use as image measuring instruments for cerebral functions in recent years.
These devices have an advantage of measuring intracerebral active areas in the form of images on the one hand. On the other hand, they have an disadvantage of being large-sized and requiring complicated handling procedures. For example, installation of these devices requires large room specifically designed for their use. It goes without saying that relocation of the devices is practically impossible. Further, an examinee is confined in a device and is required to keep the same posture for a long time during the measurement. Further, the examinee has to endure severe psychological pain in addition to this heavy physical restriction. Further, such devices require special personnel assigned for maintenance and management, with the result that huge costs will be involved in the operation of the system.
By contrast, optical measurement provides an effective means to ensure easy measurement of in-vivo blood circulation, hemodynamics and oxygen metabolism without giving much restriction to examinee or being hazardous to living body. The first reason is that the blood circulation and oxygen metabolism of the living body correspond to the concentration and its change of specific pigments (hemoglobin, cytochrome, mioglobin, etc.) in the living body, and the concentration of these pigments can be obtained from the light absorbency index of the wavelength from visible to infrared ray ranges. Said blood circulation and oxygen metabolism correspond to the normal/abnormal state of the in-vivo organs and activation of the brain with respect to high order cerebral functions. The second reason to account for effective optical measurement is that the device can be the downsized and simplified by the technologies related to semiconductor laser, light emitting diode and photodiode. Further, the head need not be fixed in position during measurement by use of flexible optical fiber for measurement. This greatly reduces the restriction on the examinee and minimizes psychological pains. The third reason is that light intensity is kept within the Safety Standard (ANSIZ 136-1973, JISC6802 Standard: 2 mW/mm2). Thus, the living body is not harmed by application of the light.
In addition to these advantages, optical measurement has advantages which cannot be found in said PET, MRI or MEG, for example, real time measurement, quantification of the concentration of pigment in the living body.
For example, the Japanese Patent Laid-Open NO. 115232/1982 and Japanese Patent Laid-Open NO. 275323/1988 disclose and claim a system wherein light with wave lengths from visible to infrared ray ranges is applied to the living body by effective use of the advantages of optical measurement, and in-vivo measurement is achieved by detecting the light passing through the living body by reflection therein. Further, a system of converting the living body in images by optical measurement is disclosed and claimed in the Japanese Patent Laid-Open NO. 19408/1997 and Japanese Patent Laid-Open NO. 149903/1997. The usefulness of image measurement of the living body using said light is also described, for example, in Atsushi Maki, et al. xe2x80x9cSpatial and temporal analysis of human motor activity using noninvasive NIR topographyxe2x80x9d, 1995, Medical Physics, Vol. 22, P.P. 1997 to 2005).
Generally, high time resolution and high-precision measurement are essential factors in the measurement of living bodies. In the system disclosed in said Japanese Patent Laid-Open NO. 149903/1997, a high time resolution is achieved by simultaneous measurement of multiple wavelengths required to measure the image of changes in the concentration of the living body pigment such as hemoglobin and multiple channels at multiple positions. FIG. 14 shows the over view of the system disclosed in the Japanese Patent Laid-Open NO. 149903/1997. This system allows light to be applied to multiple positions of the examinee, and detects light at the multiple positions.
In this case, the intensity of light is modulated at the frequency different for each of the positions where light is applied. For example, modulation frequencies for the light applied from light applied positions 1, 2, 3 and 4 in FIG. 14 are assumed as f1, f2, f3 and f4, respectively. Therefore, these modulation frequencies provide position information corresponding to each position where light is applied. Here the light detected at light detection position 1 includes all the modulated light. For signals output from the photodiode, however, light measurement signal on position information can be separately measured by selective measurement of each modulation frequency signal in a filter circuit of the lock-in amplifier or the like. For example, when each detection signal levels by modulation frequencies f1, f2, f3 and f4 detected by the photodiode corresponding to this light detection position 1 are assumed as I1, I2, I3 and I4, each signal is completely separated from others in the output of each lock-in amplifier synchronized at each frequency. As a result, effective simultaneous multi-channel measurement can be implemented since there is no crosstalk between measurement signals.
To get the final image from such measurement, however, a high measurement precision is required for each signal. If these detection signals contains a signal whose precision or S/N ratio is considerably low, for example, reliability of the measurement site corresponding to the signal will be reduced on the image, and this will lead to reliability of the image itself. This requires high-precision measurement with satisfactory S/N balance for all detection signals. However, the conventional devices have the following problems with respect to this measurement precision:
The state in the living body is optically uneven in normal cases. If arrangement is so made that light is to be applied to the site containing a large quantity of hemoglobins as light absorbers such as large blood vessel or light is detected at such a site, there will be attenuation of light and a considerable reduction in said detection signal level. Thus, another cause for reduction of the detection signal level in a particular measuring channel can be found in cases where there is a problem with the state of optical fiber installation, for example, where the end face of the optical fiber used for measurement is contaminated optically, or a hair is sandwiched between the optical fiber and the skin of the examinee head.
The following describes the how the S/N ratio of measurement is affected when there is an imbalance in the measurement signal level as a whole, including the detection signal with partially weak intensity as described above:
Normally, the shock noise of the light detector such as photodiode is proportional to light reaching a light detector, in other words, to the square root of the total sum of the detected light intensity. Here let us consider the case where the signal levels of I1, I2 and I3 are almost the same (I1xcx9cI2xcx9cI3), in detected signal levels I1, I2, I3 and I4 detected at the light detection position 1 in FIG. 14, and signal level I4 alone is smaller by an order of magnitude (I1 greater than  greater than I4). This state is assumed to occur when there is a large blood vessel close to the light applied position 4, or there is any problem installation of an optical fiber at said light applied position 4. In this case, noise due to a photodiode largely is proportional to the square root of (I1+I2+I3+I4). So level I4 which is intrinsically a signal level is heavily affected by stronger signal levels I1, I2 and I3, with the result that the S/N ratio is conspicuously reduced. To give further explanation to this point, let us take up an example where signal levels I1, I2 and I3 are further increased, with signal level I4 remaining unchanged. For level I4 in this case, noise level N will increase although the signal level, namely, S does not change.
As a result, signal S/N ratio is further deteriorated for I4. For stronger signal levels I1, I2 and I3, the S/N ratio increased. Therefore, when one optical detector is used to detect multiple optical signals, a conspicuous difference in the S/N ratio may occur between measurement channels.
In such a measurement, the following issue also occurs: In the presence of multiple strong detection signal signals, the total sum of these detection light may exceed the dynamic range due to limited dynamic range of the optical detector and lock-in amplifier and others. Said dynamic range is normally defined within the range where the linear response of the detector is ensured. However, even if the signal level has exceeded said dynamic range, a certain finite value is issued from the detector normally. But the reliability of measurement is very low for the value in this case.
As discussed above, if there is a big difference between detection signal levels, the signal S/N ratio differs greatly according to each signal. If these signals are used for imaging, image reliability will deteriorate. If these signals contain any strong detection light signal, the dynamic range of the detector will be exceeded, with the result that reliability of measurement will deteriorate.
The purpose of the present invention is to provide an optical measuring instrument suitable for multi-channel simultaneous measurement.
One object of the present invention is to provide an optical measuring instrument to generate multi-channel signals to characterize a test object by optical measurement of said test object;
said optical measuring instrument further characterized by comprising
a measuring means to perform said measurement and a preparatory measuring means to prepare for final measurement;
wherein said preparatory measuring means further comprises
a generating means to generate multi-channel signals to characterize said test object by optical measurement of said test object and
an adjusting means to adjust the generated multi-channel signals so that the level differences of said signals are kept within the specified range.
Another object of the present invention is to provide an optical measuring instrument wherein light is applied to multiple positions of the test object, and the light passing through said test object is detected and measured thereby;
said optical measuring instrument further characterized by comprising a measuring means to perform said measurement and a preparatory measuring means to prepare for final measurement;
wherein said preparatory measuring means further comprises
a means to apply said light sequentially to said multiple positions and
a means to detect the light passing through said test object by said application of light and to generate detection signal for each of said light applied positions, thereby measuring said detection signal level.
Still another object of the present invention is to provide an optical measuring instrument characterized in that light of multiple wavelengths is applied to a test object and light passing through the test object is detected and measured;
wherein said optical measuring instrument comprises
a measuring means to perform said measurement and a preparatory measuring means to prepare for final measurement;
said preparatory measuring means further comprises
a means to apply said light sequentially to said test object for each of said wavelengths and
a means to detect the light passing through said test object by said application of light and to generate detection signal for each of said wavelengths, thereby measuring said detection signal level.
A further object of the present invention is to provide an optical measuring instrument characterized by comprising a means to apply light of multiple wavelengths to multiple positions of test object, and a means to detect and measure the light passing through said test object by said application of light;
said optical measuring instrument further characterized in comprising a control unit to control said light intensity level and said detection signal level so that the level differences of said detection signals are kept within the specified range, when;
said light is applied sequentially to each of said positions for light application and for each of said wavelengths prior to the final measurement,
the light passing through said test object by said application of light is detected and is converted into electric signals,
detection signals are generated for each of said positions for light application and for each of said wavelengths based on said electric signals, and a preparatory measurement is made for said detection signal level.